| Affiliation: | 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, 999078 P. R. China
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health Bethesda, Bethesda, MD, 20892 USA;2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health Bethesda, Bethesda, MD, 20892 USA;3. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, 999078 P. R. China;4. Yong Loo Lin School of Medicine, Faculty of Engineering, National University of Singapore, Singapore, 119228 Singapore |
| Abstract: | Immunological tolerance induced by the hypoxic tumor microenvironment has been a major challenge for current immune checkpoint blockade therapies. Here, a hypoxia-responsive drug delivery nanoplatform is reported to promote chemoimmunotherapy of cancer by overcoming the hypoxia-induced immunological tolerance of tumors. The nanovesicles are assembled from manganese ferrite nanoparticles (MFNs) grafted with hypoxia-responsive amphiphilic polymers as the membrane, with doxorubicin hydrochloride (Dox) loaded in the aqueous cavities. Under hypoxic conditions in tumors, the nanovesicles can rapidly dissociate into individual MFNs to release Dox and induce decomposition of tumor endogenous H2O2 for tumor hypoxia relief. As a result, the Dox-loaded nanovesicles display remarkable suppression of primary tumor growth in combination with αPD-L1-mediated checkpoint blockade therapy. Furthermore, the modulation of the hypoxic tumor microenvironment facilitates a long-lasting immunological memory effect to prevent tumor recurrence and metastasis. Therefore, this hypoxia-responsive nanoplatform presents a potential strategy for both local tumor treatment and long-term protection against tumor recurrence. |
